Method and arrangement for filling a sterile container

ABSTRACT

Method for filling a sterile container, in particular a bottle, with a liquid, wherein a sterile connection is established between a flexible bag and a first opening of the container, a sterile connection is established between a second opening of the container and a source of the liquid to be filled into the container, the liquid is filled into the container, a gas, in particular air, which is present in the container is displaced by the liquid and forced into the flexible bag while increasing the volume of the flexible bag and the connection between the source of liquid and the second opening of the container is severed in a sterile way.

The present invention concerns a method and an arrangement for filling asterile container, such as a bottle, with a liquid.

In the pharmaceutical industry obviously strict requirements regardingsterility of any container holding substances which are used in orresult from the production process have to be fulfilled. This includesfor example bottles, which can be sterilized easily enough.

However, when such containers are filled with a liquid, a problem occursbecause the liquid displaces a gas, such as air, which is present in thecontainer before the filling process and this displaced gas has to beremoved from the container without compromising the sterility of thecontainer.

In the prior art air filters are used. Unlike usual filters, these areused to avoid outside substances, in particular micro-organisms andother contaminants to enter the bottle while the gas is dischargedthrough the filter. Naturally, these filters need to have some sort ofopenings in order to allow the displaced gas to leave the container.Even though these openings are made extremely small (e.g. less than 0.2micrometres) there exists a risk of contamination such that apost-integrity test of the air filter is needed and a confirmation ofsterility can only be granted after this post-use test, with the risk ofa failed test upon which the liquid in the bottle has to be discharged.Furthermore, this test obviously constitutes additional effort andcosts.

The object of the invention is to provide a method and an arrangementfor filling a container, such as a bottle, in such a way that nointegrity test of an air filter or the like after the filling process isnecessary.

Regarding the method this object is achieved with the features of claim1, wherein

-   -   a sterile connection is established between a flexible bag and a        first opening of the container,    -   a sterile connection is established between a second opening of        the container and a source of the liquid to be filled into the        container,    -   the liquid is filled into the container,    -   a gas, in particular air, which is present in the container is        displaced by the liquid and forced into the flexible bag while        increasing the volume of the flexible bag and    -   the connection between the source of liquid and the second        opening of the container is severed in a sterile way.

Regarding the arrangement the object is achieved with the features ofclaim 6. The arrangement according to the invention comprises thesterile container and a sterile flexible bag, wherein

-   -   the flexible bag is in fluid communication with the container        via a first opening of the container,    -   the container comprises a second opening and a sealed connecting        device for connecting in a sterile way the container to a source        of liquid to be filled into the container.

The basic idea of the invention is to use a flexible bag—which canattain different filling volumes—as an intermediate “storage” for thedisplaced gas volume. This solves the object of the invention becausedisconnecting the flexible bag after filling it with gas such that theoriginal container is not contaminated is very easy—at least compared todirectly discharging the displaced gas into the environment.

In other words, the invention makes it possible to fill a bottle withoutany external opening, and hence in a fully closed manner.

The invention can be used on any container with so much rigidity suchthat the removal of displaced gas during the filling process is aconcern (e.g. because the container would be damaged or the fillingprocess would not be possible due to the increase in pressure, if thedisplaced gas would not be removed).

A main example of containers which can be filled according to theinvention would be sterile bottles e.g. made from glass or various sortsof plastics.

The flexible bag can also be made of plastic or the like. Particularlypreferable may be embodiments, where the flexible bag is made of plasticfoils which are welded together on boundaries to form the bag.

An arrangement according to the invention has the advantage that itcould be provided as one sterile set or kit (where the flexible bag isalready connected to the container). For filling the container it isonly necessary to connect the source for liquid, fill the container anddisconnect the flexible bag as well as the source. The container isvirtually guaranteed to be sterile and no integrity checks of thecontainer are necessary, which was previously believed to be simplyimpossible.

The flexible bag can be discarded, or recycled, or kept on the bottlefor a draining process in the next process steps, e.g. if closeddraining of the bottle is required. For that the excess air/gas is inthe connected flexible bag can be used to displace the liquid from thebottle.

In particular, the first opening and the second opening of the containermay particularly preferably be separate openings, i.e. they would begeometrically distant from each other. Embodiments where the firstopening and the second opening are the same opening of the container arehowever in principle conceivable.

Under connections between the first or second opening on the one handand the flexible bag or the source for the liquid on the other hand itcan be understood that fluid communication is established.

The connection between the first opening of the container and theflexible bag can be established before, after and/or at the same time asthe connection between the second opening and the source is established.

Severing these connections in a sterile way means that the possibilityof fluid communication is stopped without introducing the possibility ofa contamination of the container (e.g. using sterile connectors orfusing tubing shut).

In particularly preferred embodiments the flexible bag and/or the sourcefor the liquid can also be detached after the connection is severed.

The invention can be used for filling any container with liquid beingused in or resulting from a pharmaceutical, in particularbiopharmaceutical, production process.

Further advantageous embodiments are defined in the dependent claims.

In particularly preferred embodiments the connection between theflexible bag and the first opening of the container can be severed in asterile way. Otherwise, the flexible bag can in principle also be kept(i.e. stored or transported) together with the container.

Severing the connection between the first opening of the container andthe flexible bag can be performed before, after and/or at the same timeas the connection between the second opening and the source is severed.

For the connection between the flexible bag and the first opening of thecontainer tubing and/or a sterile connector is used, which are bothreadily available. Sterile connectors are devices which allow for a(usually one time) sterile connection between two (or more) tubes. Bothsuch tubing and sterile connectors can be made mainly of different sortsof plastics.

Analogous measures can be taken for the connection between the secondopening and the source of liquid.

The connection between the first opening of the container and theflexible bag or the connection between the second opening of thecontainer and the source of liquid may for example be severed by fusingand/or welding shut tubing or by decoupling a sterile connector. Fusingtubing shut or welding tubing shut is a simple and reliable process.

In very simple embodiments the severing of the connections between firstor second opening and flexible bag or source for liquid can be achievedby closing clamps around connecting tubing and optionally cutting thetubing on the distal side (from the first or second opening) of theclamp.

The sealed connecting device comprised in the arrangement according tothe invention can for example be a sterile connector (or part thereof).

The sealed connecting device avoids contamination of the containerbefore the filling process begins. In the simplest embodiments thesealed connecting device can just be a sealed length of tubing or thelike.

A so-called “single use bag” (usually used for storing and/ortransporting (bio-) pharmaceutical liquids) or a similar bag can be useda flexible bag.

Further details and advantages of the invention are apparent from thefigures and the accompanying figure description. The figures showschematically:

FIG. 1 an arrangement according to the invention with the containerconnected to a source of liquid,

FIG. 2 an arrangement according to the invention,

FIG. 3 a the arrangement of FIG. 1 after filling the container and

FIG. 3 b the flexible bag in a side view.

FIG. 1 shows an arrangement comprising a container 1 in the form of abottle, e.g. made from glass or plastic. A first opening 4 of the bottleis connected to the flexible bag 3 via tubing 8 (e.g. made also fromplastic).

A second opening 5 of the bottle is connected to a source 6 of liquid 2to be filled into the bottle. Also for this connection tubing 8 is used.

Additionally, in this embodiment a sterile connector 9 is used tofacilitate a very easy connecting and/or disconnecting of the source 6with/from the bottle in a sterile manner.

The arrangement shown in FIG. 1 can particularly easily be achieved ifthe arrangement shown in FIG. 2 is provided as a set or kit, such thatonly the source 6 for the liquid 2 needs to be connected to the secondopening 5 of the bottle (e.g. via the sterile connector 9), in order tostart the filling process.

The situation after the filling of the bottle is depicted in FIGS. 3 aand 3 b . The bottle (i.e. container 1) is now filled with the liquid 2and the gas 8 (e.g. air) displaced from the bottle has made its way intothe flexible bag 3.

As shown schematically in FIG. 3 b by a dashed line, viewed from theside the flexible bag 3 has been “blown up”, i.e. increased in volume,in order to accommodate the displaced gas 8.

The source 6 and the flexible bag 3 can now easily be disconnected (i.e.the connections can be severed) and the container 1 is sterile withoutthe need for any integrity testing.

1. Method for filling a sterile container, in particular a bottle, witha liquid (2), wherein a sterile connection is established between aflexible bag and a first opening of the container, a sterile connectionis established between a second opening of the container and a source ofthe liquid to be filled into the container, the liquid is filled intothe container, a gas, in particular air, which is present in thecontainer is displaced by the liquid and forced into the flexible bagwhile increasing the volume of the flexible bag and the connectionbetween the source of liquid and the second opening of the container issevered in a sterile way.
 2. The method according to claim 1, whereinthe connection between the flexible bag and the first opening of thecontainer is severed in a sterile way.
 3. The method according to claim1, wherein for the connection between the flexible bag and the firstopening of the container tubing and/or a sterile connector is used. 4.The method according to claim 1, wherein for the connection between thesecond opening and the source of liquid tubing and/or a sterileconnector is used.
 5. The method according to claim 1, wherein theconnection between the first opening of the container and the flexiblebag or the connection between the second opening of the container andthe source of liquid is severed by fusing and/or welding shut tubingand/or decoupling a sterile connector.
 6. Arrangement for filling asterile container, in particular a bottle, comprising the sterilecontainer and a sterile flexible bag, wherein the flexible bag is influid communication with the container via a first opening of thecontainer, the container comprises a second opening and a sealedconnecting device for connecting in a sterile way the container to asource of liquid to be filled into the container.
 7. The arrangementaccording to claim 6, wherein the sealed connecting device is a sterileconnector.